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Articles 61 - 81 of 81
Full-Text Articles in Neurosciences
Rabies Screen Reveals Gpe Control Of Cocaine-Triggered Plasticity., Kevin T. Beier, Christina K. Kim, Paul Hoerbelt, Lin Wai Hung, Boris D. Heifets, Katherine E. Deloach, Timothy J. Mosca, Sophie Neuner, Karl Deisseroth, Liqun Luo, Robert C. Malenka
Rabies Screen Reveals Gpe Control Of Cocaine-Triggered Plasticity., Kevin T. Beier, Christina K. Kim, Paul Hoerbelt, Lin Wai Hung, Boris D. Heifets, Katherine E. Deloach, Timothy J. Mosca, Sophie Neuner, Karl Deisseroth, Liqun Luo, Robert C. Malenka
Department of Neuroscience Faculty Papers
Identification of neural circuit changes that contribute to behavioural plasticity has routinely been conducted on candidate circuits that were preselected on the basis of previous results. Here we present an unbiased method for identifying experience-triggered circuit-level changes in neuronal ensembles in mice. Using rabies virus monosynaptic tracing, we mapped cocaine-induced global changes in inputs onto neurons in the ventral tegmental area. Cocaine increased rabies-labelled inputs from the globus pallidus externus (GPe), a basal ganglia nucleus not previously known to participate in behavioural plasticity triggered by drugs of abuse. We demonstrated that cocaine increased GPe neuron activity, which accounted for the …
Calcineurin Dysregulation Underlies Spinal Cord Injury-Induced K(+) Channel Dysfunction In Drg Neurons., Benjamin M. Zemel, Tanziyah Muqeem, Eric V. Brown, Miguel Goulão, Mark W Urban, Stephen R. Tymanskyj, Angelo C. Lepore, Manuel Covarrubias
Calcineurin Dysregulation Underlies Spinal Cord Injury-Induced K(+) Channel Dysfunction In Drg Neurons., Benjamin M. Zemel, Tanziyah Muqeem, Eric V. Brown, Miguel Goulão, Mark W Urban, Stephen R. Tymanskyj, Angelo C. Lepore, Manuel Covarrubias
Department of Neuroscience Faculty Papers
Dysfunction of the fast-inactivating Kv3.4 potassium current in dorsal root ganglion (DRG) neurons contributes to the hyperexcitability associated with persistent pain induced by spinal cord injury (SCI). However, the underlying mechanism is not known. In light of our previous work demonstrating modulation of the Kv3.4 channel by phosphorylation, we investigated the role of the phosphatase calcineurin (CaN) using electrophysiological, molecular, and imaging approaches in adult female Sprague Dawley rats. Pharmacological inhibition of CaN in small-diameter DRG neurons slowed repolarization of the somatic action potential (AP) and attenuated the Kv3.4 current. Attenuated Kv3.4 currents also exhibited slowed inactivation. We observed similar …
Δfosb Regulates Gene Expression And Cognitive Dysfunction In A Mouse Model Of Alzheimer's Disease., Brian F Corbett, Jason C You, Xiaohong Zhang, Mark S Pyfer, Umberto Tosi, Daniel M Iascone, Iraklis Petrof, Anupam Hazra, Chia-Hsuan Fu, Gabriel S Stephens, Annie Ashok, Suzan Aschmies, Lijuan Zhao, Eric J Nestler, Jeannie Chin
Δfosb Regulates Gene Expression And Cognitive Dysfunction In A Mouse Model Of Alzheimer's Disease., Brian F Corbett, Jason C You, Xiaohong Zhang, Mark S Pyfer, Umberto Tosi, Daniel M Iascone, Iraklis Petrof, Anupam Hazra, Chia-Hsuan Fu, Gabriel S Stephens, Annie Ashok, Suzan Aschmies, Lijuan Zhao, Eric J Nestler, Jeannie Chin
Department of Neuroscience Faculty Papers
Alzheimer's disease (AD) is characterized by cognitive decline and 5- to 10-fold increased seizure incidence. How seizures contribute to cognitive decline in AD or other disorders is unclear. We show that spontaneous seizures increase expression of ΔFosB, a highly stable Fos-family transcription factor, in the hippocampus of an AD mouse model. ΔFosB suppressed expression of the immediate early gene c-Fos, which is critical for plasticity and cognition, by binding its promoter and triggering histone deacetylation. Acute histone deacetylase (HDAC) inhibition or inhibition of ΔFosB activity restored c-Fos induction and improved cognition in AD mice. Administration of seizure-inducing agents to nontransgenic …
A Role For Ankyring In Maturation And Maintenance Of The Nodes Of Ranvier., Benjamin Yang, Bridget M. Curran, Stephen R. Tymanskyj
A Role For Ankyring In Maturation And Maintenance Of The Nodes Of Ranvier., Benjamin Yang, Bridget M. Curran, Stephen R. Tymanskyj
Department of Neuroscience Faculty Papers
No abstract provided.
Presynaptic Lrp4 Promotes Synapse Number And Function Of Excitatory Cns Neurons., Timothy J. Mosca, David J. Luginbuhl, Irving E. Wang, Liqun Luo
Presynaptic Lrp4 Promotes Synapse Number And Function Of Excitatory Cns Neurons., Timothy J. Mosca, David J. Luginbuhl, Irving E. Wang, Liqun Luo
Department of Neuroscience Faculty Papers
Precise coordination of synaptic connections ensures proper information flow within circuits. The activity of presynaptic organizing molecules signaling to downstream pathways is essential for such coordination, though such entities remain incompletely known. We show that LRP4, a conserved transmembrane protein known for its postsynaptic roles, functions presynaptically as an organizing molecule. In the Drosophila brain, LRP4 localizes to the nerve terminals at or near active zones. Loss of presynaptic LRP4 reduces excitatory (not inhibitory) synapse number, impairs active zone architecture, and abolishes olfactory attraction - the latter of which can be suppressed by reducing presynaptic GABAB receptors. LRP4 overexpression increases …
Identification Of Octopaminergic Neurons That Modulate Sleep Suppression By Male Sex Drive., Daniel R. Machado, Dinis Afonso, Alexandra R. Kenny, Arzu Öztürk-Çolak, Emilia H. Moscato, Benjamin Mainwaring, Matthew Kayser, Kyunghee Koh
Identification Of Octopaminergic Neurons That Modulate Sleep Suppression By Male Sex Drive., Daniel R. Machado, Dinis Afonso, Alexandra R. Kenny, Arzu Öztürk-Çolak, Emilia H. Moscato, Benjamin Mainwaring, Matthew Kayser, Kyunghee Koh
Department of Neuroscience Faculty Papers
Molecular and circuit mechanisms for balancing competing drives are not well understood. While circadian and homeostatic mechanisms generally ensure sufficient sleep at night, other pressing needs can overcome sleep drive. Here, we demonstrate that the balance between sleep and sex drives determines whether male flies sleep or court, and identify a subset of octopaminergic neurons (MS1) that regulate sleep specifically in males. When MS1 neurons are activated, isolated males sleep less, and when MS1 neurons are silenced, the normal male sleep suppression in female presence is attenuated and mating behavior is impaired. MS1 neurons do not express the sexually dimorphic …
Map7 Regulates Axon Collateral Branch Development In Dorsal Root Ganglion Neurons., Stephen R Tymanskyj, Benjamin Yang, Aditi Falnikar, Angelo C Lepore, Le Ma
Map7 Regulates Axon Collateral Branch Development In Dorsal Root Ganglion Neurons., Stephen R Tymanskyj, Benjamin Yang, Aditi Falnikar, Angelo C Lepore, Le Ma
Department of Neuroscience Faculty Papers
Collateral branches from axons are key components of functional neural circuits that allow neurons to connect with multiple synaptic targets. Like axon growth and guidance, formation of collateral branches depends on the regulation of microtubules, but how such regulation is coordinated to ensure proper circuit development is not known. Based on microarray analysis, we have identified a role for microtubule-associated protein 7 (MAP7) during collateral branch development of dorsal root ganglion (DRG) sensory neurons. We show that MAP7 is expressed at the onset of collateral branch formation. Perturbation of its expression by overexpression or shRNA knockdown alters axon branching in …
Regulation Of Sleep Plasticity By A Thermo-Sensitive Circuit In Drosophila., Angelique Lamaze, Arzu Öztürk-Çolak, Robin Fischer, Nicolai Peschel, Kyunghee Koh, James E.C. Jepson
Regulation Of Sleep Plasticity By A Thermo-Sensitive Circuit In Drosophila., Angelique Lamaze, Arzu Öztürk-Çolak, Robin Fischer, Nicolai Peschel, Kyunghee Koh, James E.C. Jepson
Department of Neuroscience Faculty Papers
Sleep is a highly conserved and essential behaviour in many species, including the fruit fly Drosophila melanogaster. In the wild, sensory signalling encoding environmental information must be integrated with sleep drive to ensure that sleep is not initiated during detrimental conditions. However, the molecular and circuit mechanisms by which sleep timing is modulated by the environment are unclear. Here we introduce a novel behavioural paradigm to study this issue. We show that in male fruit flies, onset of the daytime siesta is delayed by ambient temperatures above 29 °C. We term this effect Prolonged Morning Wakefulness (PMW). We show that …
Pathogenic Determinants And Mechanisms Of Als/Ftd Linked To Hexanucleotide Repeat Expansions In The C9orf72 Gene., Xinmei Wen, Thomas Westergard, Piera Pasinelli, Davide Trotti
Pathogenic Determinants And Mechanisms Of Als/Ftd Linked To Hexanucleotide Repeat Expansions In The C9orf72 Gene., Xinmei Wen, Thomas Westergard, Piera Pasinelli, Davide Trotti
Department of Neuroscience Faculty Papers
Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are two apparently distinct neurodegenerative diseases, the former characterized by selective loss of motor neurons in the brain and spinal cord and the latter characterized by selective atrophy of frontal and temporal lobes. Over the years, however, growing evidence from clinical, pathological and genetic findings has suggested that ALS and FTD belong to the same clinic-pathological spectrum disorder. This concept has been further supported by the identification of the most common genetic cause for both diseases, an aberrantly expanded hexanucleotide repeat GGGGCC/ CCCCGG sequence located in a non-coding region of the gene …
Harnessing The Power Of Cell Transplantation To Target Respiratory Dysfunction Following Spinal Cord Injury., Brittany A. Charsar, Mark W. Urban, Angelo C. Lepore
Harnessing The Power Of Cell Transplantation To Target Respiratory Dysfunction Following Spinal Cord Injury., Brittany A. Charsar, Mark W. Urban, Angelo C. Lepore
Department of Neuroscience Faculty Papers
The therapeutic benefit of cell transplantation has been assessed in a host of central nervous system (CNS) diseases, including disorders of the spinal cord such as traumatic spinal cord injury (SCI). The promise of cell transplantation to preserve and/or restore normal function can be aimed at a variety of therapeutic mechanisms, including replacement of lost or damaged CNS cell types, promotion of axonal regeneration or sprouting, neuroprotection, immune response modulation, and delivery of gene products such as neurotrophic factors, amongst other possibilities. Despite significant work in the field of transplantation in models of SCI, limited attention has been directed at …
Assessment Of The Effects Of Mptp And Paraquat On Dopaminergic Neurons And Microglia In The Substantia Nigra Pars Compacta Of C57bl/6 Mice., Richard Jay Smeyne, Charles B. Breckenridge, Melissa Beck, Yun Jiao, Mark T. Butt, Jeffrey C. Wolf, Dan Zadory, Daniel J. Minnema, Nicholas C. Sturgess, Kim Z. Travis, Andrew R. Cook, Lewis L. Smith, Philip A. Botham
Assessment Of The Effects Of Mptp And Paraquat On Dopaminergic Neurons And Microglia In The Substantia Nigra Pars Compacta Of C57bl/6 Mice., Richard Jay Smeyne, Charles B. Breckenridge, Melissa Beck, Yun Jiao, Mark T. Butt, Jeffrey C. Wolf, Dan Zadory, Daniel J. Minnema, Nicholas C. Sturgess, Kim Z. Travis, Andrew R. Cook, Lewis L. Smith, Philip A. Botham
Department of Neuroscience Faculty Papers
The neurotoxicity of paraquat dichloride (PQ) was assessed in two inbred strains of 9- or 16-week old male C57BL/6 mice housed in two different laboratories and compared to the effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). PQ was administered by intraperitoneal injections; either once (20 mg/kg) or twice (10 mg/kg) weekly for 3 weeks, while MPTP-HCl was injected 4 times on a single day (20 mg/kg/dose). Brains were collected 8, 16, 24, 48, 96 or 168 hours after the last PQ treatment, and 48 or 168 hours after MPTP treatment. Dopamine neurons in the substantia nigra pars compacta (SNpc) were identified by antibodies …
Tau Phosphorylation At Alzheimer's Disease-Related Ser356 Contributes To Tau Stabilization When Par-1/Mark Activity Is Elevated., Kanae Ando, Mikiko Oka, Yosuke Ohtake, Motoki Hayashishita, Sawako Shimizu, Shin-Ichi Hisanaga, Koichi M. Iijima
Tau Phosphorylation At Alzheimer's Disease-Related Ser356 Contributes To Tau Stabilization When Par-1/Mark Activity Is Elevated., Kanae Ando, Mikiko Oka, Yosuke Ohtake, Motoki Hayashishita, Sawako Shimizu, Shin-Ichi Hisanaga, Koichi M. Iijima
Department of Neuroscience Faculty Papers
Abnormal phosphorylation of the microtubule-associated protein tau is observed in many neurodegenerative diseases, including Alzheimer's disease (AD). AD-related phosphorylation of two tau residues, Ser262 and Ser356, by PAR-1/MARK stabilizes tau in the initial phase of mismetabolism, leading to subsequent phosphorylation events, accumulation, and toxicity. However, the relative contribution of phosphorylation at each of these sites to tau stabilization has not yet been elucidated. In a Drosophila model of human tau toxicity, we found that tau was phosphorylated at Ser262, but not at Ser356, and that blocking Ser262 phosphorylation decreased total tau levels. By contrast, when PAR-1 was co-overexpressed with tau, …
Closed-State Inactivation Involving An Internal Gate In Kv4.1 Channels Modulates Pore Blockade By Intracellular Quaternary Ammonium Ions., Jeffrey D. Fineberg, Tibor G. Szanto, Gyorgy Panyi, Manuel Covarrubias
Closed-State Inactivation Involving An Internal Gate In Kv4.1 Channels Modulates Pore Blockade By Intracellular Quaternary Ammonium Ions., Jeffrey D. Fineberg, Tibor G. Szanto, Gyorgy Panyi, Manuel Covarrubias
Department of Neuroscience Faculty Papers
Voltage-gated K(+) (Kv) channel activation depends on interactions between voltage sensors and an intracellular activation gate that controls access to a central pore cavity. Here, we hypothesize that this gate is additionally responsible for closed-state inactivation (CSI) in Kv4.x channels. These Kv channels undergo CSI by a mechanism that is still poorly understood. To test the hypothesis, we deduced the state of the Kv4.1 channel intracellular gate by exploiting the trap-door paradigm of pore blockade by internally applied quaternary ammonium (QA) ions exhibiting slow blocking kinetics and high-affinity for a blocking site. We found that inactivation gating seemingly traps benzyl-tributylammonium …
Stabilization Of Microtubule-Unbound Tau Via Tau Phosphorylation At Ser262/356 By Par-1/Mark Contributes To Augmentation Of Ad-Related Phosphorylation And Aβ42-Induced Tau Toxicity., Kanae Iijima-Ando, Akiko Maruko-Otake, Yosuke Ohtake, Motoki Hayashishita, Michiko Sekiya, Koichi M Iijima
Stabilization Of Microtubule-Unbound Tau Via Tau Phosphorylation At Ser262/356 By Par-1/Mark Contributes To Augmentation Of Ad-Related Phosphorylation And Aβ42-Induced Tau Toxicity., Kanae Iijima-Ando, Akiko Maruko-Otake, Yosuke Ohtake, Motoki Hayashishita, Michiko Sekiya, Koichi M Iijima
Department of Neuroscience Faculty Papers
Abnormal accumulation of the microtubule-interacting protein tau is associated with neurodegenerative diseases including Alzheimer's disease (AD). β-amyloid (Aβ) lies upstream of abnormal tau behavior, including detachment from microtubules, phosphorylation at several disease-specific sites, and self-aggregation into toxic tau species in AD brains. To prevent the cascade of events leading to neurodegeneration in AD, it is essential to elucidate the mechanisms underlying the initial events of tau mismetabolism. Currently, however, these mechanisms remain unclear. In this study, using transgenic Drosophila co-expressing human tau and Aβ, we found that tau phosphorylation at AD-related Ser262/356 stabilized microtubule-unbound tau in the early phase of …
Loss Of Vglut3 Produces Circadian-Dependent Hyperdopaminergia And Ameliorates Motor Dysfunction And L-Dopa-Mediated Dyskinesias In A Model Of Parkinson's Disease., Christopher B. Divito, Kathy Steece-Collier, Daniel T. Case, Sean-Paul G. Williams, Jennifer A. Stancati, Lianteng Zhi, Maria E. Rubio, Caryl E. Sortwell, Timothy J. Collier, David Sulzer, Robert H. Edwards, Hui Zhang, Rebecca P. Seal
Loss Of Vglut3 Produces Circadian-Dependent Hyperdopaminergia And Ameliorates Motor Dysfunction And L-Dopa-Mediated Dyskinesias In A Model Of Parkinson's Disease., Christopher B. Divito, Kathy Steece-Collier, Daniel T. Case, Sean-Paul G. Williams, Jennifer A. Stancati, Lianteng Zhi, Maria E. Rubio, Caryl E. Sortwell, Timothy J. Collier, David Sulzer, Robert H. Edwards, Hui Zhang, Rebecca P. Seal
Department of Neuroscience Faculty Papers
UNLABELLED: The striatum is essential for many aspects of mammalian behavior, including motivation and movement, and is dysfunctional in motor disorders such as Parkinson's disease. The vesicular glutamate transporter 3 (VGLUT3) is expressed by striatal cholinergic interneurons (CINs) and is thus well positioned to regulate dopamine (DA) signaling and locomotor activity, a canonical measure of basal ganglia output. We now report that VGLUT3 knock-out (KO) mice show circadian-dependent hyperlocomotor activity that is restricted to the waking cycle and is due to an increase in striatal DA synthesis, packaging, and release. Using a conditional VGLUT3 KO mouse, we show that deletion …
Taranis Functions With Cyclin A And Cdk1 In A Novel Arousal Center To Control Sleep In Drosophila., Dinis J.S. Afonso, Die Liu, Daniel R. Machado, Huihui Pan, James E.C. Jepson, Dragana Rogulja, Kyunghee Koh
Taranis Functions With Cyclin A And Cdk1 In A Novel Arousal Center To Control Sleep In Drosophila., Dinis J.S. Afonso, Die Liu, Daniel R. Machado, Huihui Pan, James E.C. Jepson, Dragana Rogulja, Kyunghee Koh
Department of Neuroscience Faculty Papers
Sleep is an essential and conserved behavior whose regulation at the molecular and anatomical level remains to be elucidated. Here, we identify TARANIS (TARA), a Drosophila homolog of the Trip-Br (SERTAD) family of transcriptional coregulators, as a molecule that is required for normal sleep patterns. Through a forward-genetic screen, we isolated tara as a novel sleep gene associated with a marked reduction in sleep amount. Targeted knockdown of tara suggests that it functions in cholinergic neurons to promote sleep. tara encodes a conserved cell-cycle protein that contains a Cyclin A (CycA)-binding homology domain. TARA regulates CycA protein levels and genetically …
Defects In Synapse Structure And Function Precede Motor Neuron Degeneration In Drosophila Models Of Fus-Related Als., Mohammad Shahidullah, Sylvain J Le Marchand, Hong Fei, Jiaming Zhang, Udai Bhan Pandey, Matthew B. Dalva, Piera Pasinelli, Irwin B. Levitan
Defects In Synapse Structure And Function Precede Motor Neuron Degeneration In Drosophila Models Of Fus-Related Als., Mohammad Shahidullah, Sylvain J Le Marchand, Hong Fei, Jiaming Zhang, Udai Bhan Pandey, Matthew B. Dalva, Piera Pasinelli, Irwin B. Levitan
Department of Neuroscience Faculty Papers
Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease that leads invariably to fatal paralysis associated with motor neuron degeneration and muscular atrophy. One gene associated with ALS encodes the DNA/RNA-binding protein Fused in Sarcoma (FUS). There now exist two Drosophila models of ALS. In one, human FUS with ALS-causing mutations is expressed in fly motor neurons; in the other, the gene cabeza (caz), the fly homolog of FUS, is ablated. These FUS-ALS flies exhibit larval locomotor defects indicative of neuromuscular dysfunction and early death. The locus and site of initiation of this neuromuscular dysfunction remain unclear. We show here …
Expression Of C-Fos In Hilar Mossy Cells Of The Dentate Gyrus In Vivo., Aine M Duffy, Michael J Schaner, Jeannie Chin, Helen E Scharfman
Expression Of C-Fos In Hilar Mossy Cells Of The Dentate Gyrus In Vivo., Aine M Duffy, Michael J Schaner, Jeannie Chin, Helen E Scharfman
Department of Neuroscience Faculty Papers
Granule cells (GCs) of the dentate gyrus (DG) are considered to be quiescent--they rarely fire action potentials. In contrast, the other glutamatergic cell type in the DG, hilar mossy cells (MCs) often have a high level of spontaneous activity based on recordings in hippocampal slices. MCs project to GCs, so activity in MCs could play an important role in activating GCs. Therefore, we investigated whether MCs were active under basal conditions in vivo, using the immediate early gene c-fos as a tool. We hypothesized that MCs would exhibit c-fos expression even if rats were examined randomly, under normal housing conditions. …
Degeneration Of Phrenic Motor Neurons Induces Long-Term Diaphragm Deficits Following Mid-Cervical Spinal Contusion In Mice., Charles Nicaise, Rajarshi Putatunda, Tamara J Hala, Kathleen A Regan, David M Frank, Jean-Pierre Brion, Karelle Leroy, Roland Pochet, Megan C Wright, Angelo C Lepore
Degeneration Of Phrenic Motor Neurons Induces Long-Term Diaphragm Deficits Following Mid-Cervical Spinal Contusion In Mice., Charles Nicaise, Rajarshi Putatunda, Tamara J Hala, Kathleen A Regan, David M Frank, Jean-Pierre Brion, Karelle Leroy, Roland Pochet, Megan C Wright, Angelo C Lepore
Department of Neuroscience Faculty Papers
A primary cause of morbidity and mortality following cervical spinal cord injury (SCI) is respiratory compromise, regardless of the level of trauma. In particular, SCI at mid-cervical regions targets degeneration of both descending bulbospinal respiratory axons and cell bodies of phrenic motor neurons, resulting in deficits in the function of the diaphragm, the primary muscle of inspiration. Contusion-type trauma to the cervical spinal cord is one of the most common forms of human SCI; however, few studies have evaluated mid-cervical contusion in animal models or characterized consequent histopathological and functional effects of degeneration of phrenic motor neuron-diaphragm circuitry. We have …
Human Glial-Restricted Progenitor Transplantation Into Cervical Spinal Cord Of The Sod1 Mouse Model Of Als., Angelo C Lepore, John O'Donnell, Andrew S Kim, Timothy Williams, Alicia Tuteja, Mahendra S Rao, Linda L Kelley, James T Campanelli, Nicholas J Maragakis
Human Glial-Restricted Progenitor Transplantation Into Cervical Spinal Cord Of The Sod1 Mouse Model Of Als., Angelo C Lepore, John O'Donnell, Andrew S Kim, Timothy Williams, Alicia Tuteja, Mahendra S Rao, Linda L Kelley, James T Campanelli, Nicholas J Maragakis
Department of Neuroscience Faculty Papers
Cellular abnormalities are not limited to motor neurons in amyotrophic lateral sclerosis (ALS). There are numerous observations of astrocyte dysfunction in both humans with ALS and in SOD1(G93A) rodents, a widely studied ALS model. The present study therapeutically targeted astrocyte replacement in this model via transplantation of human Glial-Restricted Progenitors (hGRPs), lineage-restricted progenitors derived from human fetal neural tissue. Our previous findings demonstrated that transplantation of rodent-derived GRPs into cervical spinal cord ventral gray matter (in order to target therapy to diaphragmatic function) resulted in therapeutic efficacy in the SOD1(G93A) rat. Those findings demonstrated the feasibility and efficacy of transplantation-based …
Slob, A Slowpoke Channel Binding Protein, Regulates Insulin Pathway Signaling And Metabolism In Drosophila., Amanda L. Sheldon, Jiaming Zhang, Hong Fei, Irwin B Levitan
Slob, A Slowpoke Channel Binding Protein, Regulates Insulin Pathway Signaling And Metabolism In Drosophila., Amanda L. Sheldon, Jiaming Zhang, Hong Fei, Irwin B Levitan
Department of Neuroscience Faculty Papers
There is ample evidence that ion channel modulation by accessory proteins within a macromolecular complex can regulate channel activity and thereby impact neuronal excitability. However, the downstream consequences of ion channel modulation remain largely undetermined. The Drosophila melanogaster large conductance calcium-activated potassium channel SLOWPOKE (SLO) undergoes modulation via its binding partner SLO-binding protein (SLOB). Regulation of SLO by SLOB influences the voltage dependence of SLO activation and modulates synaptic transmission. SLO and SLOB are expressed especially prominently in median neurosecretory cells (mNSCs) in the pars intercerebralis (PI) region of the brain; these cells also express and secrete Drosophila insulin like …